The goals of the proposed research are (1) to determine and characterize the processes that are involved in transmitter release by developing quantitative description of the effect of repetitive stimulation on transmitter release, (2) to investigate the mechanisms of facilitation, augmentation, and potentiation (three processes that act to increase transmitter release) by looking for differential effects of external (Ca ions), (Sr ions), (Ba ions), (Mg ions), (Na ions), changes in osmolarity, and mitochondrial inhibitors on these three processes, facilitation, augmentation, and potantiation, is associated with a change in the statistical release parameters n and/or p from the quantal hypothesis of transmitter release. Depending on the experiment, estimates of the relative amount of transmitter release at the vertebrate neuromuscular junction will be made from measurements of end-plate potentials recorded intracellularly or extracellularly or from measurements of end-plate currents recorded under voltage clamp. Models for the mechanism of transmitter release will be formulated and evaluated by comparing experimental results with predicted resulted obtained by stimulation of the proposed mechanisms of release on a digital computer.